Ion trap mass spectrometers are well known in the art for analysis of a wide variety of substances. When operating an ion trap, it is desirable to maintain the number of ion charges in the trap (the number of ions times the charge/ion) at or near a target value in order to optimize trap performance. Overfilling the ion trap results in space charge effects that adversely affect resolution and mass accuracy; conversely, under-filling the ion trap reduces sensitivity. A number of approaches have been described in the prior art for optimizing ion population. The “automatic gain control” (AGC) method discussed in U.S. Pat. No. 5,572,022 (incorporated herein by reference) involves calculation of the fill time (also referred to as the injection time) of an ion trap based on the ion flux over a mass range of interest so that the ion trap is filled with a fixed number of charges that approximates the number that produces optimal trap performance. The ion flux is determined by performing a “pre-scan” in which the ion trap is filled over a short predetermined injection time, and accumulated ions are then scanned out of the trap to measure the resultant total number of charges. From this measured ion flux, the appropriate injection time can be calculated for the actual analytical scan. To retain the quantitative capability of the system, the resultant intensities can be appropriately scaled by accounting for the specific injection used to acquire each spectrum.
Ion traps, as well as other mass analyzers, may also be operated in a so-called “data-dependent” mode, in which an analytical scan of interest over an extended mass-to-charge (m/z) range (a full scan) is immediately followed by one or more MS/MS or MSn experiments on ions selected and isolated based on the full-scan results, e.g., on the N most intense peaks in the full-scan mass spectrum. The terms “MS/MS” and “MSn” refer to mass analysis experiments in which a particular precursor ion is selected and isolated at the first stage of analysis or in a first mass analyzer (MS-1), the precursor ions are subjected to fragmentation (e.g. in a collision cell, which may also function as an ion accumulator), and the resulting fragment (product) ions are analyzed in a second stage of analysis or in a second mass analyzer (MS-2). The method can be extended to provide fragmentation of a selected fragment, and so on, with analysis of the resulting fragments for each generation. This is typically referred to an MSn spectrometry, with the superscript “n” indicating the number of steps of mass analysis and the number of generations of ions, and is a somewhat unique capability for trapping types of mass analyzers. Accordingly, MS2 corresponds to two stages of mass analysis with two generations of ions analyzed (precursor and products).
An important parameter in the operation of mass spectrometers is the cycle time, which is how long it takes to perform a particular scan type and is often expressed as the number of mass scan events that can be acquired in a one-second time window. It can be readily concluded that the need to conduct a pre-scan before each data-dependent experiment adversely impacts the cycle time of the ion trap.
U.S. Pat. No. 7,312,441 (also incorporated by reference) describes a method, referred to as “predictive AGC”. In predictive AGC, the intensity of a peak in the full scan spectrum corresponding to an ion of interest and the ion fill time for the full scan are used to calculate the fill time required for the data-dependent scan on the ion of interest. A problem may arise with the practice of predictive AGC when ion injections for the full scan and data-dependent scan are performed under different injection conditions. As used herein, the term “injection conditions” refers to any parameter or combination of parameters that affects the efficiency of transmission of ions from the ion source to the ion trap and/or the efficiency of trapping of ions within the ion trap, including but not limited to the values of voltages applied to various ion optical elements and parameters defining injection voltage waveforms applied to the electrodes of the ion trap itself Generally, for a given set of parameters, the efficiency of ion injection can be dependent on the m/z of a particular ion species; for example, ions having a relatively large m/z may be injected at greater efficiency relative to ions of lower m/z or vice versa. It may be beneficial to select the ion injection parameters based on objectives for a given type of experiment. For example, it is generally desirable to obtain a substantially flat (m/z invariant) injection curve for full-scan experiments so that the mass spectrum accurately reflects the relative quantities of the wide m/z range of ions produced in the ion source, whereas for data-dependent experiments it may be desirable to optimize transmission just for the precursor ion species of interest.
U.S. Patent Application Publication No. US2009/0045062 (also incorporated herein by reference) provides an illustration of how different injection conditions may be utilized for filling ion traps for full-scan and data-dependent experiments. This publication describes the operation of a stacked ring ion guide (SRIG) ion transport device, which assists in the transport of analyte ions in the low vacuum region of the mass spectrometer. The relevant injection parameter is the amplitude of the RF voltage applied to the stack of ring electrodes. During a full-scan experiment, the RF voltage amplitude is stepped over, for instance, three values during the injection period in order to obtain a substantially flat aggregate transmission curve in the m/z range of interest. In contrast, for data-dependent experiments, the RF voltage is set to maximize the transmission efficiency for the selected precursor ion species. If the predictive AGC method is employed in these circumstances, the data-dependent experiment injection time calculated based on the intensity of the selected ion peak in the full-scan mass spectrum and the full-scan injection time will be excessive (owing to the differences in the transmission efficiencies of the selected ion during the full-scan and data-dependent experiments), resulting in space charging of the ion trap and the consequential detrimental effects.
As a result of the foregoing discussions, it is clear that there is a need in the art for methods which are able to compensate for mass spectrometer systems having ion transfer optics whose transmission efficiency is m/z-dependent and to correct the injection times calculated for data-dependent MS/MS or MSn experiments in which the precursor ion intensities in the preceding full scan are used to calculate the injection times for the subsequent MS/MS or MSn scans. The previously-described AGC and predictive AGC techniques are not fully adequate for such situations. Embodiments in accordance with the present teachings address the foregoing deficiencies of the predictive AGC technique. The invention is illustrated herein in connection with its application to operation of a mass spectrometer having a SRIG ion transport device. However, the principles of the invention may be extended to any ion trap mass spectrometer having mass-selective ion optics in the ion path and in which injection conditions are separately optimized or selected for full-scan and subsequent data-dependent experiments. Without limitation, the technique may be employed for quadrupole ion traps (QITs) as well as other types of trapping mass analyzers, such as FTICR analyzers and Orbitraps or, indeed, for any ion optical elements having mass dependent transmission efficiency.